Pd-Catalyzed 2-Pyridylmethyl Transfer from 2-(2-Pyridyl)-ethanol Derivatives to Aryl Halides by Chelation-Assisted Cleavage of Csp3-Csp3 Bonds

Link: http://www3.interscience.wiley.com/cgi-bin/abstract/114134097/ABSTRACT

From Prof. Koichiro Oshima's group at Kyoto University

Palladium-Catalyzed 2-Pyridylmethyl Transfer from 2-(2-Pyridyl)-ethanol Derivatives to Organic Halides by Chelation-Assisted Cleavage of Unstrained Csp3-Csp3 Bonds

The paper presents a method for the transfer of 2-(2-pyridylmethyl) group generated by a cleavage of 2-(2-pyridyl)-ethanol as assisted by a palladium catalyst.

The authors have screened different Pd catalysts and have found Pd (II) trifluoroacetate to be the most effective. Together with tricyclohexyl phosphine ligand and cesium carbonate as a base, the authors were able to transfer the 2-(2-pyridylmethyl) group and effect its coupling with various aryl chlorides. The reaction was found to NOT work with 2-phenyl ethanol derivative, nor the 2-(4-pyridyl)-ethanol derivative. In term of coupling partners, the reaction also did not work with simple alkyl chloride, whereas allyl or benzyl chlorides only yielded complex mixture.

But the system can be employed efficiently with 1,3,5-trichlorobenzene to afford a scaffold shown below (taken from their paper) in good yield.

In addition, the reaction was found to be applicable to in transferring other derivatives of aza-aryl ethanol and coupling them with chlorobenzene in good to excellent efficiency.

The proposed mechanism was shown below (from their paper). Based on their other experiments, the nitrogen at the 2-position is needed to coordinate with palladium catalyst.

They were also able to effect an in situ carbopalladation of the N,N-diisobutenyl-2-chloroaniline and couple that intermediate with the 2-(2-pyridylmethyl) group in good yield.

This is a neat overall chemistry and, as one can see, very useful.